Project Summary Hematopoietic malignancies including leukemias and lymphomas contribute to nearly half of all cancers and are a major cause of death from disease in children. The Children?s Oncology Group (COG) has spearheaded efforts to improve outcome in children with cancer, and despite dramatic improvements in survival over the last several decades, relapse remains a major problem, and survivors may suffer long term complications from the cytotoxic therapy. Better understanding of the biology of malignancies allows for more rational, targeted approaches to therapy, minimizing the need or the intensity of the non-selective cytotoxic therapies. Such targeted approaches have transformed some diseases from uniformly fatal to highly curable ones (e.g., CML, APL), but a paucity of actionable targets has prevented broader application of targeted interventions in hematopietic malignancies. As part of its focus on optimizing the survival in pediatric cancers and improving quality of life for the cancer survivors, COG through partnerships with NCI has conducted a number of discovery phase studies to identify the biologic basis of cancer in children, with the goal of identifying specific targets for more appropriate risk stratification and directed therapies in its clinical trials. With the emerging data from pediatric (and adult) discovery phase studies, COG is poised to take the next step in identifying actionable targets for therapeutic intervention. As part of these efforts, COG has created the Network Group Integrated Translational Science Centers (ITSCs) aimed at providing resources for therapeutically driven translational research. COG Hematopoietic ITSC (HM-ITSC) has put into place intellectual (leadership) and physical resources (resource laboratories, biospecimens, etc.) to ensure rapid identification of actionable targets through carefully designed translational research projects, and fostering the experimental data through a carefully structured mechanism to clinical application. HM-ITSC is structured and integrated into the functional operations of the COG, with direct links to the COG Operations Office, Disease Committees, Network group Data and Statistics Center and Developmental Therapeutics in order to facilitate rapid flow of actionable translational biology data to clinical implementation within NCTN clinical trials. Hematopoietic Malignancies (HM) are a major cause of cancer in children and novel therapeutic targets are needed to optimize outcome. COG HM-Integrated Translational Science Center, integrated into the functional organization of COG, will provide resources to support translational research in pediatric leukemias and lymphomas towards identification of clinically meaningful targets and their incorporation into clinical trials.